Acidylsalicylic acid ester and process of making same.



UNITED STATES PATENT o FioE.

RICHARD WOLFFENSTEIN, OF BERLIN, GERMANY;

A CIDYLSALICYLIC ACID ESTER AND PROCESS OF MAKING 1,063,099. No Drawing.

To all whom it may concern s Be it known that I, RIC-HARD WOLFFEN-STEIN, a citizen of the German Empire, residing at Berlin/in the Kingdomof PMS-- sia,, Germany, haveinvented certain new and useful Improvementsin Acidylsalicylic Acid Esters and Processes of Making Same; and I dohereby declare the following to be a full, clear, and exact descriptionof the invention, such as will enable others skilled in the art to whichit appertains to make and use the same. I

My invention relates to improvements in the process of makingacidylsalicylic acid ester, and to the product produced thereby.

The production of acetylsalicylic acid esters by causing alcohols toreact on chlorid of acetylsalicylic acid, that is by the known method ofproducing esters, has been found to be impossible. For example, whentrying to produce the ethyl ester a mixture is obtained which in itsessential elements consists of salicylic acid, salicyli'ds, salicylicacid ethyl ester, and acetic ,acid ethyl ester. Therefore the reactionof the production of an ethyl ester from an acid chlorid and alcoholwhich ordinarily takes place in organic chemistry does not take place inthis case. Further experiments have shown the general fact, thatacidylized salicylic acid halog'enids can not be transformed in this wayinto esters. and that always mixtures of salicylic'acid, salicylic acidesters, salicylids. and acetic esters are produced.

I have discovered, that the hydrochloric acid which is liberated has aninjurious effect on the reaction whereby the desired ester can not beobtained, but that the reaction does take place, and the acidyl estersare produced, if care is taken, that the hydrochloric acid formed by thereaction is immediately removed. This may be done for example by meansof compounds which are adapted to bind acids, such for example astertiary bases.

In order that my invention be more clearly understood several examplesare describedhereafter.

First example: 10 grams of acetyl salicylic acid chlorid are mixed with8 grams of quinolin While cooling the same, whereupon 4 cubiccentimeters of absolute alcohol are added. .At the endof the reactionthe contents of the still are solidified into Specification of LettersPatent.

Application filed Hovember 25, 1911. Serial No. 682,45G;

' Patented May 27, 1913.

a thick pulp of crystals. The pulp is thereupon heated half an hour onthe water bath, ligroin is added, and the mixture is first shaken withdiluted hydrochloric acid, thereupon with "soda solution, and finallywith water. The solution Which is sepa+ rated from the water is driedwith dried sodium sulfate, the ligroin is distilled oil",

and finally the acetyl salicylic acid ethyl which is thus obtained isdistilled off.

The acetyl salicylic acid ethyl ester boils at a temperature of 273degrees centigrade, reacts neutrally, is readily soluble in alcohol andbenzene, difiicultly soluble in water, produces when treated with alkaliafter neutralization the well known violet color with iron chloridsolution, which is character istic for salicylic acid. As distinguishedfrom the corresponding ester of the salicylic acid its odor is much lessstrong.

Second example: 10.5 grams of acetyl propyl ester cmeooc 'rtoooon 0H,001,

which is thus obtained reacts neutrally with litmus paper. The acetylgroup is split off by alkalis, and it can easily be recognized from theviolet reaction of the product with iron chlorid. The body is easilysoluble in ligroin and in alcohol, very difficulty soluble in water. Theester is decomposed when trying to distil the same, which distillationis not even obtained in mono. Melting temperature 62 degrees centigrade.

Third example: grams of acetyl salicylic acid chlorid and 30 gr.trichlorisobutyl alcohol are dissolved in the presence of 25 grams ofcalcium carbonate in 8 cubic centimeters of benzene, heated a few hours,allowed to cool, put into a further amount of benzene, successivelyshaken with soda soluomoooo iipooown ,001,

melts at a temperature of 7 5 degrees centigrade, has a neutralreaction, can be distilled in 'zraouo at a temperature of 185 degreescentigrade un'der partial decomposition, crystallizes well, and whentreated with alkali splits ofi' the acetyl group. When lightly heatedwith concentrated sulfuric acid it gives off hydrochloric acid.

The acidylated salicylic acid esters produced as described are ofinterest by reason of their physiological action. Particularly thetrichlorisopropyl and trichlorisobutyl esters are valuable, because theycombine the anesthetic and anodyne action of their alcohols with theantirheumatic action of the salicylic acid.

I claim herein as my invention:

1. The herein described process of produc ing acidylsalicylic acidesters, which consists in causing an alcohol to act on acidylsalicylicacid halogenids and immediately rendering the hydrogen halogenic acidwhich is formed ineffective.

The herein described process of producing acidyl salicyclic acid esters,which consists in causing an alcohol to act on an acidylsalicylic acidchlorid in the presence of a medium which is adapted to bindhydrochloric acid.

3. The herein described recess of roducing acetyl salicylic acitrichlorisobutyl ester, which consists in heating acetylsalicylic acidchlorid with trichlorisobutyl alcohol and hydrochloric acid.

4. The herein described process of producing acetylsalicylic acidtrichlorisobutyl ester, which consists in dissolving acetylsalicylicacid chlorid and trichlorisobutyl alcohol in the presence of calciumcarbonate in benzene, .heatin the solution, allowing the same to cool,issolving the product in benzene, successively shaking with dilutedhydrochloric acid, soda solution, and water, and recrystallizing theproduct.

5. As a new product, the herein described acetyl salicylic acidtrichlorisobutyl ester, which crystallizes in needles, melts at atemperature of 7 5 degrees centigrade, boils under partial decompositionin vacuo at a temperature of about 185 degrees Centigrade, is readilysoluble in the usual organic solvents, insoluble in water, has a neutralreaction, splits ofi salicylic acid when heated with alkali. and givesoff hydrochloric acid when heated with concentrated sulfuric acid.

RICHARD WOLFFENSTEIN.

\Vitnesses:

ARTHUR MARnUsE, HENRY HASPER.

a medium which is adapted to bind

